1 Ocak 2023 Dergi makalesi Açık Erişim

Wijesinghe, Tharushi P.; Kaya, Busra; Gonzalvez, Miguel A.; Harmer, Jeffrey R.; Gholam Azad, Mahan; Bernhardt, Paul V.; Dharmasivam, Mahendiran; Richardson, Des R.

JSON

{
  "conceptrecid": "271193", 
  "created": "2024-06-07T16:30:43.970076+00:00", 
  "doi": "10.1021/acs.jmedchem.3c01612", 
  "files": [
    {
      "bucket": "292efa2d-6bdb-41f1-9131-222b3e9dcc46", 
      "checksum": "md5:79d25c5d117b1993789e4a60257aceb1", 
      "key": "bib-39813977-68c4-4f4d-a289-f50bad3ec3b5.txt", 
      "links": {
        "self": "https://aperta.ulakbim.gov.tr/api/files/292efa2d-6bdb-41f1-9131-222b3e9dcc46/bib-39813977-68c4-4f4d-a289-f50bad3ec3b5.txt"
      }, 
      "size": 304, 
      "type": "txt"
    }
  ], 
  "id": 271194, 
  "links": {
    "badge": "https://aperta.ulakbim.gov.tr/badge/doi/10.1021/acs.jmedchem.3c01612.svg", 
    "bucket": "https://aperta.ulakbim.gov.tr/api/files/292efa2d-6bdb-41f1-9131-222b3e9dcc46", 
    "doi": "https://doi.org/10.1021/acs.jmedchem.3c01612", 
    "html": "https://aperta.ulakbim.gov.tr/record/271194", 
    "latest": "https://aperta.ulakbim.gov.tr/api/records/271194", 
    "latest_html": "https://aperta.ulakbim.gov.tr/record/271194"
  }, 
  "metadata": {
    "access_right": "open", 
    "access_right_category": "success", 
    "communities": [
      {
        "id": "tubitak-destekli-proje-yayinlari"
      }
    ], 
    "creators": [
      {
        "affiliation": "Griffith Univ, Griffith Inst Drug Discovery, Ctr Canc Cell Biol & Drug Discovery, Brisbane, Qld 4111, Australia", 
        "name": "Wijesinghe, Tharushi P."
      }, 
      {
        "affiliation": "Griffith Univ, Griffith Inst Drug Discovery, Ctr Canc Cell Biol & Drug Discovery, Brisbane, Qld 4111, Australia", 
        "name": "Kaya, Busra"
      }, 
      {
        "affiliation": "Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia", 
        "name": "Gonzalvez, Miguel A."
      }, 
      {
        "affiliation": "Univ Queensland, Ctr Adv Imaging, Brisbane, Qld 4072, Australia", 
        "name": "Harmer, Jeffrey R."
      }, 
      {
        "affiliation": "Griffith Univ, Griffith Inst Drug Discovery, Ctr Canc Cell Biol & Drug Discovery, Brisbane, Qld 4111, Australia", 
        "name": "Gholam Azad, Mahan"
      }, 
      {
        "affiliation": "Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld 4072, Australia", 
        "name": "Bernhardt, Paul V."
      }, 
      {
        "affiliation": "Griffith Univ, Griffith Inst Drug Discovery, Ctr Canc Cell Biol & Drug Discovery, Brisbane, Qld 4111, Australia", 
        "name": "Dharmasivam, Mahendiran"
      }, 
      {
        "name": "Richardson, Des R."
      }
    ], 
    "description": "<p>The di-2-pyridylketone thiosemicarbazones demonstrated marked anticancer efficacy, prompting progression of DpC to clinical trials. However, DpC induced deleterious oxy-myoglobin oxidation, stifling development. To address this, novel substituted phenyl thiosemicarbazone (PPP4pT) analogues and their Fe-(III), Cu-(II), and Zn-(II) complexes were prepared. The PPP4pT analogues demonstrated potent antiproliferative activity (IC50: 0.009-0.066 mu M), with the 1:1 Cu:L complexes showing the greatest efficacy. Substitutions leading to decreased redox potential of the PPP4pT:Cu-(II) complexes were associated with higher antiproliferative activity, while increasing potential correlated with increased redox activity. Surprisingly, there was no correlation between redox activity and antiproliferative efficacy. The PPP4pT:Fe-(III) complexes attenuated oxy-myoglobin oxidation significantly more than the clinically trialed thiosemicarbazones, Triapine, COTI-2, and DpC, or earlier thiosemicarbazone series. Incorporation of phenyl- and styryl-substituents led to steric blockade, preventing approach of the PPP4pT:Fe-(III) complexes to the heme plane and its oxidation. The 1:1 Cu-(II):PPP4pT complexes were inert to transmetalation and did not induce oxy-myoglobin oxidation.</p>", 
    "doi": "10.1021/acs.jmedchem.3c01612", 
    "has_grant": false, 
    "journal": {
      "issue": "22", 
      "pages": "24", 
      "title": "JOURNAL OF MEDICINAL CHEMISTRY", 
      "volume": "66"
    }, 
    "license": {
      "id": "cc-by"
    }, 
    "publication_date": "2023-01-01", 
    "relations": {
      "version": [
        {
          "count": 1, 
          "index": 0, 
          "is_last": true, 
          "last_child": {
            "pid_type": "recid", 
            "pid_value": "271194"
          }, 
          "parent": {
            "pid_type": "recid", 
            "pid_value": "271193"
          }
        }
      ]
    }, 
    "resource_type": {
      "subtype": "article", 
      "title": "Dergi makalesi", 
      "type": "publication"
    }, 
    "science_branches": [
      "Di\u011fer"
    ], 
    "title": "Steric Blockade of Oxy-Myoglobin Oxidation by Thiosemicarbazones: Structure-Activity Relationships of the Novel PPP4pT Series"
  }, 
  "owners": [
    1
  ], 
  "revision": 1, 
  "stats": {
    "downloads": 0.0, 
    "unique_downloads": 0.0, 
    "unique_views": 0.0, 
    "version_downloads": 0.0, 
    "version_unique_downloads": 0.0, 
    "version_unique_views": 0.0, 
    "version_views": 0.0, 
    "version_volume": 0.0, 
    "views": 0.0, 
    "volume": 0.0
  }, 
  "updated": "2024-06-07T16:30:44.006082+00:00"
}